Sarcopenia in chronic kidney disease

Factors, mechanisms, and therapeutic interventions

Hiroshi Watanabe, Yuki Enoki, Toru Maruyama

Research output: Contribution to journalArticle

Abstract

Chronic kidney disease (CKD), a chronic catabolic condition, is characterized by muscle wasting and decreased muscle endurance. Many insights into the molecular mechanisms of muscle wasting in CKD have been obtained. A persistent imbalance between protein degradation and synthesis in muscle causes muscle wasting. During muscle wasting, high levels of reactive oxygen species (ROS) and inflammatory cytokines are detected in muscle. These increased ROS and inflammatory cytokine levels induce the expression of myostatin. The myostatin binding to its receptor activin A receptor type IIB stimulates the expression of atrogenes such as atrogin-1 and muscle ring factor 1, members of the muscle-specific ubiquitin ligase family. Impaired mitochondrial function also contributes to reducing muscle endurance. The increased protein-bound uremic toxin, parathyroid hormone, glucocorticoid, and angiotensin II levels that are observed in CKD all have a negative effect on muscle mass and endurance. Among the protein-bound uremic toxins, indoxyl sulfate, an indole-containing compound has the potential to induce muscle atrophy by stimulating ROS-mediated myostatin and atrogenes expression. Indoxyl sulfate also impairs mitochondrial function. Some potential therapeutic approaches based on the muscle wasting mechanisms in CKD are currently in the testing stages.

Original languageEnglish
Pages (from-to)1437-1445
Number of pages9
JournalBiological and Pharmaceutical Bulletin
Volume42
Issue number9
DOIs
Publication statusPublished - 2019 Jan 1

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Sarcopenia
Chronic Renal Insufficiency
Muscles
Myostatin
Therapeutics
Indican
Reactive Oxygen Species
Cytokines
Muscular Atrophy
Ligases
Ubiquitin
Parathyroid Hormone
Angiotensin II
Glucocorticoids
Proteolysis

Keywords

  • Indoxyl sulfate
  • Mitochondria
  • Muscle wasting
  • Myostatin
  • Oxidative stress
  • Uremic toxin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Sarcopenia in chronic kidney disease : Factors, mechanisms, and therapeutic interventions. / Watanabe, Hiroshi; Enoki, Yuki; Maruyama, Toru.

In: Biological and Pharmaceutical Bulletin, Vol. 42, No. 9, 01.01.2019, p. 1437-1445.

Research output: Contribution to journalArticle

Watanabe, Hiroshi ; Enoki, Yuki ; Maruyama, Toru. / Sarcopenia in chronic kidney disease : Factors, mechanisms, and therapeutic interventions. In: Biological and Pharmaceutical Bulletin. 2019 ; Vol. 42, No. 9. pp. 1437-1445.
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